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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
other information
Study period:
June 9th, 1999 to July 13th, 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
92/69/EEC
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
February 24th, 1987
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method

Test material

Test material form:
solid
Specific details on test material used for the study:
Purity: 96.0 % [w/w]

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Origin of test animals: Harlan Winkelmann GmbH, Gartenstraße 27, D33178 Borchen
SPF breeding colony
Body weight at the start of study:
Male animals 231-284 g, mean 255 g, S.D. +/- 17.7 g
Female animals 196-219 g, mean 209 g, S.D. +/- 8.7 g
Age at the start of study: 6-10 weeks

Acclimatization: at least seven days
Food: ssniff® R/M-H (V 1534), ad libitum
Photoperiod: 12 hours light / dark cycle
Relative humidity: 50 ± 20 %
Room temperature: 22 ± 3°C
Water: tap water in plastic bottles, ad libitum
Animal maintenance: in transparent macrolon® cages (type 3) on soft wood granulate in an
airconditioned room, 1 animal per cage

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Remarks:
0.1 mL deionized water per 0.5 g test substance
Details on dermal exposure:
Before dermal treatment the fur was mechanically removed from the dorsal skin of the animals over an area of approximately 30 cm².
The appropriate amount of the test substance was moistened on a two-ply gauze and an aluminium foil (6 x 8 cm) and distributed as uniformly as possible. Together with the foil the test substance was administered to the shaved and intact dorsal skin. The foil was held in place with an elastic plaster bandage fixed around the animal's body.
Duration of exposure:
24 hours
Doses:
160, 200, 315 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
The test substance preparations were administered by gavage to fasted animals at the stated dosage. The observation period following treatment lasted for 14 days. Symptoms and lethality were recorded twice every day (in the morning and in the afternoon). Animals found dead were dissected as soon as possible and examined for macroscopically visible changes.

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
> 160 - <= 315 mg/kg bw
Based on:
test mat.
Mortality:
Male animals, dose 160 mg/kg bw: 0/5
Male animals, dose 200 mg/kg bw: 3/5
Male animals, dose 315 mg/kg bw: 5/5
Female animals, dose 200 mg/kg bw: 2/5
Female animals, dose 315 mg/kg bw: 5/5
Clinical signs:
other: Lethality occurred up to day three of the study. Besides unspecific symptoms the animals showed impairments of mobility and respiration, narrowed palpebral fissures, squatting posture, stupor, twitching, trembling, tonoclonic convulsion and diarrhea. At d
Gross pathology:
Necropsy of the decedent animals revealed red discoloured lungs and the small intestine full of yellow mucus. Additionally, one female animal showed red discoloured small intestine.
The animals killed at the end of the observation period showed no macroscopically visible changes.

Applicant's summary and conclusion

Interpretation of results:
Category 2 based on GHS criteria
Conclusions:
Based on the results of this study the median lethal dose value (LD50) of Tetrakis(piperidino)phosphonium chloride is between 160 and 315 mg/kg body weight in male rats.